The potential use of quantum dots (QD) as a medical diagnostic tool, as well as in other biomedical applications, has led to concern regarding their toxicity, potential systemic distribution, and biopersistence. In addition, little is known about workplace exposure to QD, such as research, manufacturing, or medical settings. We have shown that pulmonary exposure to functionalized QD caused a dose-dependent increase in lung injury and inflammation which persisted up to 28 days. The goal of the present study was to assess the biodistribution of QD in rats after pulmonary exposure. QD were composed of a cadmium-selenium (CdSe) core (approximately 5nm) with a zinc sulfide (ZnS) shell functionalized with carboxyl (COOH-QD) or amine (NH2-QD) terminal groups Male Sprague-Dawley rats were intratracheally-instilled (IT) with saline, COOH-QD, or NH2-QD (12.5 ug/rat). On days 0, 1, 3, 7, 14, and 28 post-IT, the left lung, lung-associated lymph nodes (LALN), heart, kidneys, spleen, liver, brain, and blood were collected for metal analysis of Cd content by neutron activation. Right lungs from rats in each group were either subjected to bronchoalveolar lavage (BAL) to retrieve BAL fluid and cells for analysis of damage, or were preserved and sectioned for histopathology, confocal imaging, and autometallographic silver enhancement of Cd. No Cd was detected in the liver, spleen, heart, brain, or blood at any time point. At days 7 and 14, when lung injury and inflammation were at their greatest, approximately 3-5 % of the total Cd instilled was detected in the LALN of rats treated with COOH-QD, and approximately 10-20% was located in the kidney in these rats. By day 14, Cd was also found to be present in the kidneys of rats treated with NH2-QD. Both forms of QD caused significant lung injury and inflammation, with particles present in alveolar macrophages, on epithelial surfaces, and in the interstitium, which persisted in the lungs up to 28 days post-exposure. QD are not readily cleared from the lungs after IT and translocation to other organs appears to be related to damage to the air-blood barrier.
Biological-distribution; Biological-effects; Biological-function; Biological-systems; Biological-transport; Breathing; Exposure-assessment; Exposure-levels; Exposure-methods; Immune-reaction; Immune-system; Immunotoxins; Lung-disorders; Lung-irritants; Lung-fibrosis; Lung-function; Laboratory-animals; Particle-aerodynamics; Particulate-dust; Pulmonary-disorders; Pulmonary-function; Pulmonary-system; Pulmonary-system-disorders; Respiratory-hypersensitivity; Respiratory-irritants; Respiratory-system-disorders; Statistical-analysis
The Toxicologist. Society of Toxicology 48th Annual Meeting and ToxExpo, March 15-19, 2009, Baltimore, Maryland